Two cyclin-dependent kinase pathways are essential for polarized trafficking of presynaptic components

Chan Yen Ou, Vivian Y. Poon, Celine I. Maeder, Shigeki Watanabe, Emily K. Lehrman, Amy K.Y. Fu, Mikyoung Park, Wing Yu Fu, Erik M. Jorgensen, Nancy Y. Ip, Kang Shen

Research output: Contribution to journalArticlepeer-review

Abstract

Polarized trafficking of synaptic proteins to axons and dendrites is crucial to neuronal function. Through forward genetic analysis in C. elegans, we identified a cyclin (CYY-1) and a cyclin-dependent Pctaire kinase (PCT-1) necessary for targeting presynaptic components to the axon. Another cyclin-dependent kinase, CDK-5, and its activator p35, act in parallel to and partially redundantly with the CYY-1/PCT-1 pathway. Synaptic vesicles and active zone proteins mostly mislocalize to dendrites in animals defective for both PCT-1 and CDK-5 pathways. Unlike the kinesin-3 motor, unc-104/Kif1a mutant, cyy-1 cdk-5 double mutants have no reduction in anterogradely moving synaptic vesicle precursors (SVPs) as observed by dynamic imaging. Instead, the number of retrogradely moving SVPs is dramatically increased. Furthermore, this mislocalization defect is suppressed by disrupting the retrograde motor, the cytoplasmic dynein complex. Thus, PCT-1 and CDK-5 pathways direct polarized trafficking of presynaptic components by inhibiting dynein-mediated retrograde transport and setting the balance between anterograde and retrograde motors.

Original languageEnglish (US)
Pages (from-to)846-858
Number of pages13
JournalCell
Volume141
Issue number5
DOIs
StatePublished - May 2010
Externally publishedYes

Keywords

  • Molneuro

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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